The study of cell differentiation using the human multipotential cell line K-562 is a model for the study of stem cell differentiation in human leukemia cells. The K-562 leukemia cell line was originally established by us with blasts from a CML in terminal blast crisis. The results of work in progress indicate that the K-562 blasts are multipotential leukemic cells that can undergo either spontaneous or induced differentiation along the erythrocytic, granulocytic, monocytic, lymphocytic, and the megakaryocytic series. The specific aims are: (1) to study the potential for differentiation of different sublines and clones of K-562 blasts into progenitors of the five bone marrow cell series. By means of in vitro assays, we study morphologic and biologic changes associated with cell differentiation. The procedures followed employ biological response modifiers and inducers of differentiation (differones) such as hemin, dimethylsulfoxide, retinoids antigens, DNA inhibitors, differentiation factors, growth factors, thymic factor and thymic hormones, interleukins 1 and 2, and specific antibodies including monoclonal antibodies; (2) to assess if the K-562 cells lose their characteristic malignancy at some stage of differentiation and maturation; (3) to evaluate if the karyotypic characteristics including the Ph1 chromosome and other markers present in a hypodiploid and near triploid K-562 blasts are modified during differentiation and maturation; (4) to determine if differentiated K-562 cells without the specific chromosome markers still proliferate in vitro (50 to find out if K-562 have a change in leukemia-associated antigen expression during differentiation); (5) to explore whether an alteration of antigenic determinants also involves natural killer cells; and (6) to study the resistance, if any, of K-562 leukemic cells to lipid peroxidation, a phenomenon observed in most neoplastic cells but not in normal cells. This research requires expertise in tissue culture, hematology, cytogenetics, oncology, pathology, and immunology. The results of this project may provide new knowledge on new therapeutic modalities for myelogenous, lymphoid, or erythroid types of human leukemia. (M)